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One candidate gene investigated due to its association with AUD is the dopamine D4 receptor gene (<jats:italic>DRD4<\/jats:italic>), which contains a 48\u2013base pair variable number tandem repeat (<jats:italic>VNTR)<\/jats:italic> in exon 3 of its coding region. To date, no quantitative synthesis of the published literature on the effects of <jats:italic>DRD4 VNTR<\/jats:italic> variation on alcohol\u2010related phenotypes has been conducted. MEDLINE, Embase, Web of Science, and PsycInfo were searched for studies that reported on alcohol craving, alcohol consumption, severity of AUD, and case\u2010control (AUD versus no diagnosis of AUD) studies in DRD4L (seven repeats or more) carriers compared with DRD4S (six repeats or less) homozygotes. Random\u2010effects meta\u2010analysis was used for all analyses. A pooled sample size of 655 to 13,360 of 28 studies were included. Compared with DRD4S homozygotes, DRD4L carriers had increased number of drinking days (SMD: 0.205; 95% CI: 0.008 to 0.402), binge drinking days (SMD: 0.217; 95% CI: 0.0532 to 0.380), and severity of AUD (SMD: 0.143; 95% CI: 0.028\u00a0to\u00a00.259). There was no difference between <jats:italic>DRD4 VNTR<\/jats:italic> genotypes on drinks per drinking day, largest number of drinks per day\/occasion, and case\u2010control analysis. It was not possible to conduct a meta\u2010analysis of the craving data, but a systematic review of this literature found mixed results on <jats:italic>DRD4 VNTR<\/jats:italic> genotype effect. The present meta\u2010analysis suggests <jats:italic>DRD4 VNTR<\/jats:italic> variation may be a risk factor for problematic alcohol use. Our findings are limited, however, by the absence of ancestry data from studies included in our analysis, precluding our ability to adjust for population stratification. Due to the likelihood of type I error in candidate gene approaches, our work highlights the critical need for studies with larger and more inclusive samples that account for sex and genetic ancestry to fully understand this relationship.<\/jats:p>","DOI":"10.1111\/adb.12770","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T11:50:21Z","timestamp":1559303421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Parsing out the role of dopamine D4 receptor gene (DRD4) on alcohol\u2010related phenotypes: A meta\u2010analysis and systematic review"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8964-8326","authenticated-orcid":false,"given":"Allison M.","family":"Daurio","sequence":"first","affiliation":[{"name":"Department of Psychology Florida State University  Tallahassee FL USA"},{"name":"Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Basic Research and National Institute on Drug Abuse Intramural Research Program National Institutes of Health  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara L.","family":"Deschaine","sequence":"additional","affiliation":[{"name":"Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Basic Research and National Institute on Drug Abuse Intramural Research Program National Institutes of Health  Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amirhossein","family":"Modabbernia","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Seaver Autism Center Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-8754","authenticated-orcid":false,"given":"Lorenzo","family":"Leggio","sequence":"additional","affiliation":[{"name":"Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Basic Research and National Institute on Drug Abuse Intramural Research Program National Institutes of Health  Bethesda MD USA"},{"name":"Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences Brown University  Providence RI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291714002165"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agw046"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050166"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65031157.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012464099"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001350"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/358149a0"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/420854"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00562-8"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(99)00062-7"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2013.10.009"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30340"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2008.00120.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1997.tb03725.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2015.01.017"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-13-154"},{"key":"e_1_2_9_18_1","unstructured":"HigginsJP.Green S. 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